A wide variety of mental and physical processes are controlled or influenced by neural activity in particular regions of the brain. The neural-functions in some areas of the brain (i.e., the sensory or motor cortices) are organized according to physical or cognitive functions. There are also several other areas of the brain that appear to have distinct functions in most individuals. In the majority of people, for example, the areas of the occipital lobes relate to vision, the regions of the left interior frontal lobes relate to language, and the regions of the cerebral cortex appear to be consistently involved with conscious awareness, memory, and intellect.
Many problems or abnormalities with body functions can be caused by damage, disease and/or disorders in the brain. Effectively treating such abnormalities may be very difficult. For example, a stroke is a very common condition that damages the brain. Strokes are generally caused by emboli (e.g., obstruction of a vessel), hemorrhages (e.g., rupture of a vessel), or thrombi (e.g., clotting) in the vascular system of a specific region of the brain, which in turn generally cause a loss or impairment of a neural function (e.g., neural functions related to facial muscles, limbs, speech, etc.). Stroke patients are typically treated using various forms of physical therapy to rehabilitate the loss of function of a limb or another affected body part. Stroke patients may also be treated using physical therapy plus an adjunctive therapy such as amphetamine treatment. For most patients, however, such treatments are minimally effective and little can be done to improve the function of an affected body part beyond the recovery that occurs naturally without intervention.
Neural activity is governed by electrical impulses or “action potentials” generated in and propagated by neurons. While in a quiescent state, a neuron is negatively polarized and exhibits a resting membrane potential that is typically between −70 and −60 mV. Through chemical connections known as synapses, any given neuron receives from other neurons excitatory and inhibitory input signals or stimuli. A neuron integrates the excitatory and inhibitory input signals it receives, and generates or fires a series of action potentials when the integration exceeds a threshold potential. A neural firing threshold may be, for example, approximately −55 mV. Action potentials propagate to the neuron's synapses, where they are conveyed to other neurons to which the neuron is synaptically connected.
The neural activity in the brain can be accordingly influenced by electrical energy that is supplied from a man-made source such as a waveform generator. Various neural functions can thus be promoted or disrupted by applying an electrical current to the cortex or other region of the brain. As a result, researchers have attempted to treat damage, disease and disorders in the brain using electrical or magnetic stimulation signals to control or affect brain functions. One treatment approach, transcranial electrical stimulation (TES), involves placing an electrode on the exterior of the scalp and delivering an electrical current to the brain through the scalp and skull. Another treatment approach, transcranial magnetic stimulation (TMS), involves producing a high-powered magnetic field adjacent to the exterior of the scalp over an area of the cortex. Yet another treatment approach involves direct electrical stimulation of neural tissue using implanted electrodes.
A neural stimulation signal may comprise a series or train of electrical or magnetic pulses that can affect neurons within a target neural population, and may be defined or described in accordance with stimulation signal parameters including pulse amplitude, pulse frequency, duty cycle, stimulation signal duration, and/or other parameters. Electrical or magnetic stimulation signals applied to a population of neurons can depolarize neurons within the population toward their threshold potentials. Depending upon stimulation signal parameters, this depolarization can cause neurons to generate or fire action potentials. Neural stimulation that elicits or induces action potentials in a functionally significant proportion of the neural population to which the stimulation is applied is referred to as supra-threshold stimulation; neural stimulation that fails to elicit action potentials in a functionally significant proportion of the neural population is defined as sub-threshold stimulation. In general, supra-threshold stimulation of a neural population triggers or activates one or more functions associated with the neural population, but sub-threshold stimulation by itself fails to trigger or activate such functions. Supra-threshold neural stimulation can induce various types of measurable or monitorable responses in a patient. For example, supra-threshold stimulation applied to a patient's motor cortex can induce muscle fiber contractions.
Although electrical or magnetic stimulation of neural tissue may be directed toward producing an intended type of therapeutic, rehabilitative, or restorative neural activity, such stimulation may result in collateral neural activity. In particular, neural stimulation delivered beyond a certain intensity, level, or amplitude can give rise to seizure activity and/or other types of collateral activity, which may be undesirable and/or inconvenient in a neural stimulation situation.
Seizure activity may originate at a seizure focus, which is a collection of neurons (e.g., on the order of 1000 neurons) exhibiting a characteristic type of synchronous firing activity. In particular, each neuron within a seizure focus exhibits a firing response known as a paroxysmal depolarizing shift (PDS). The PDS is a large magnitude, long duration depolarization that triggers a neuron to fire a train or burst of action potentials. Properly functioning feedback and/or feed-forward inhibitory signaling mechanisms cause an ensuing afterhyperpolarization, through which the neuron's membrane potential returns to a hyperpolarized state below its firing threshold. Following the afterhyperpolarization, the neuron may undergo another PDS.
The afterhyperpolarization limits the duration of the PDS, thereby helping to ensure that synchronous neural firing activity remains localized to the seizure focus. Inhibitory feedback signaling provided by neurons surrounding a seizure focus, commonly referred to as surround inhibition, is particularly important in constraining seizure activity to the seizure focus. In the event that inhibitory signaling mechanisms fail and/or are unable to overcome or counter PDS activity, neurons within the seizure focus recruit other neurons to which they are synaptically coupled into their synchronous firing pattern. As a result, synchronous firing activity spreads beyond the seizure focus to other areas of the brain. This can lead to a cascade effect in which seizure activity becomes increasingly widespread and accompanying clinical manifestations become increasingly significant.
In view of the foregoing, it may be very important in any given neural stimulation situation to determine an appropriate stimulation signal amplitude, level, or intensity. However, an appropriate stimulation signal level may vary on a per-patient basis and possibly over time for any particular patient. Notwithstanding, determination of a neural stimulation threshold corresponding to a minimum or near-minimum stimulation signal level that induces or generates a measurable or monitorable patient response can provide a reference point for establishing a stimulation signal intensity appropriate for a neural stimulation session.
Various types of neural stimulation thresholds exist. For example, an electromyography or electromyographic (EMG) threshold may be defined as a lowest or near-lowest level of neural stimulation that generates an EMG signal of a particular magnitude. An EMG signal provides a measurement of electrical discharges associated with the innervation of muscle fibers by one or more motor neurons, and the onset of muscle fiber contraction in response to such electrical discharges. As another example, a sensation threshold may be defined as a lowest or near-lowest level of neural stimulation at which a patient notices, perceives, or experiences a physical sensation such as a tingling or vibration in a muscle group or limb. As yet another example, a movement threshold may be defined as a lowest or near-lowest level of neural stimulation that induces a noticeable movement in a patient's limb.
Unfortunately, neural stimulation threshold testing can itself induce collateral neural activity. During a typical neural stimulation threshold test procedure, a very low amplitude test stimulation signal is initially applied to a patient. The amplitude of the test stimulation signal is then increased incrementally, while other test stimulation signal parameters (e.g., frequency, pulse characteristics, duty cycle, etc.) remain unchanged or unmodified. As its amplitude is increased, the test stimulation signal is delivered to the patient in an uninterrupted or continuous manner. A lowest or near-lowest test stimulation signal amplitude that evokes a given type of patient response is correspondingly defined as the neural stimulation threshold. The patient is subsequently treated using a stimulation signal having parameters identical to those of the test stimulation signal, with the possible exception of stimulation signal amplitude, which may be a predetermined value based on the neural stimulation threshold.
Stimulation signal characteristics and manners in which stimulation signals are applied to a target neural population can significantly affect the likelihood of inducing collateral neural activity. Conventional neural stimulation threshold test procedures fail to adequately address this consideration, and thus may be susceptible to inducing seizure activity and/or other types of collateral neural activity. Hence, there is a need for systems and methods that reduce the likelihood of inducing such activity during neural stimulation threshold testing.